Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China.
Shenzhen College of Advanced Technology, University of the Chinese Academy of Sciences, 100049, Beijing, China.
Nat Commun. 2023 Jun 6;14(1):3297. doi: 10.1038/s41467-023-38814-w.
Acoustic tweezers can control target movement through the momentum interaction between an acoustic wave and an object. This technology has advantages over optical tweezers for in-vivo cell manipulation due to its high tissue penetrability and strong acoustic radiation force. However, normal cells are difficult to acoustically manipulate because of their small size and the similarity between their acoustic impedance and that of the medium. In this study, we use the heterologous expression of gene clusters to generate genetically engineered bacteria that can produce numerous sub-micron gas vesicles in the bacterial cytoplasm. We show that the presence of the gas vesicles significantly enhances the acoustic sensitivity of the engineering bacteria, which can be manipulated by ultrasound. We find that by employing phased-array-based acoustic tweezers, the engineering bacteria can be trapped into clusters and manipulated in vitro and in vivo via electronically steered acoustic beams, enabling the counter flow or on-demand flow of these bacteria in the vasculature of live mice. Furthermore, we demonstrate that the aggregation efficiency of engineering bacteria in a tumour is improved by utilizing this technology. This study provides a platform for the in-vivo manipulation of live cells, which will promote the progress of cell-based biomedical applications.
声镊可以通过声波与物体之间的动量相互作用来控制目标的运动。与光学镊子相比，这种技术具有更高的组织穿透性和更强的声辐射力，因此更适合用于活体细胞操作。然而，由于正常细胞体积小，其声阻抗与介质相似，因此很难对其进行声操控。在本研究中，我们使用基因簇的异源表达来生成能够在细菌细胞质中产生大量亚微米级气腔的基因工程菌。我们发现气腔的存在显著提高了工程菌的声敏性，使其可以通过超声进行操控。我们发现，通过使用相控阵声镊，可以将工程菌捕获成簇，并通过电子控制的声束在体外和体内进行操控，从而实现在活体小鼠血管中对这些细菌的反向或按需流动。此外，我们证明了利用这项技术可以提高工程菌在肿瘤中的聚集效率。本研究为活体细胞的体内操控提供了一个平台，将促进基于细胞的生物医学应用的进展。
